Positive Phase 2 Clinical Results Showed PRO 140 Demonstrated Potent Activity, Favorable Tolerability and the Convenience of Potential Weekly Self-Administration
MONTREAL, CANADA & TARRYTOWN, NY, USA | February 10, 2009 | Progenics Pharmaceuticals, Inc. (Nasdaq: PGNX – News) today announced that it has selected for further development the subcutaneous form of PRO 140 for the treatment of HIV infection. The decision follows positive results from a recently completed phase 2 clinical trial as well as feedback from key opinion leaders, treatment advocates and people living with HIV. Results from the phase 2 study were presented late yesterday at the 16th Conference on Retroviruses and Opportunistic Infections (CROI) in Montreal. In this clinical trial, the subcutaneous dosage form of PRO 140 demonstrated potent and highly significant antiviral effects compared to placebo at all doses of active drug examined and was generally well tolerated.
“These phase 2 clinical results confirm our previously announced interim findings which showed that subcutaneous PRO 140 therapy was potent, long-acting and well tolerated,” said Paul J. Maddon, M.D., Ph.D., Progenics Pharmaceuticals’ Founder, Chief Executive Officer and Chief Science Officer. “We plan to meet with the U.S. Food and Drug Administration to discuss registrational studies for subcutaneous PRO 140. Similar to intravenous PRO 140, the subcutaneous form has demonstrated significant antiviral activity and favorable tolerability in clinical trials to date, with the additional potential benefit of convenient self-administration by patients. Given that all currently available HIV drugs are given between one and three times daily, a weekly therapy could have many advantages related to adherence.”
PRO 140 is a humanized monoclonal antibody that blocks viral infection of healthy cells by binding to CCR5, a co-receptor that is the principal molecular portal used by HIV to enter and infect immune system cells. Some strains of HIV use the CXCR4 co-receptor as a portal of entry either exclusively or in addition to CCR5. CCR5 viral-entry inhibitors, such as PRO 140, are active in blocking infection primarily in HIV patients whose virus uses the CCR5 portal, but do not block the entry of virus that uses the CXCR4 portal.
The data presented yesterday indicate that PRO 140 has the potential to be administered weekly, which may facilitate its use in conjunction with other antiretroviral therapies. In this study, all active doses of subcutaneous PRO 140 demonstrated potent and highly significant antiviral effects compared to placebo. A mean maximum reduction in plasma levels of HIV RNA of 1.65 log10 (98%) was observed following three weekly doses of 324 mg, the highest dose tested. All dose levels were generally well tolerated.
“The results of this clinical trial establish the first ever proof of concept for a long-acting HIV therapy with the potential for self-administration,” said Melanie A. Thompson M.D., Principal Investigator of the AIDS Research Consortium of Atlanta and lead author of the CROI presentation. “Given its favorable tolerability profile and potential for convenient weekly dosing by patients, subcutaneous PRO 140 holds promise in providing a potent and novel treatment option for individuals living with HIV.”
Subcutaneous PRO 140: Summary of phase 2 clinical trial results
In the phase 2 clinical trial of subcutaneous PRO 140, a total of 44 HIV-infected individuals who were treatment naïve or had discontinued therapy for at least three months were randomized to receive three weekly doses of 162 mg PRO 140, two bi-weekly (every-other-week) doses of 324 mg PRO 140, three weekly doses of 324 mg PRO 140, or placebo. Subjects were followed for a total of 58 days for safety and antiviral effects.
In this study, the following activity for PRO 140 was observed:
* For the 324 mg weekly dose group, a mean maximum reduction of 1.65 log10 (p<0.0001) was observed, with a 1.51 log10 mean reduction in viral load (p<0.0001) observed at day 22.
* For the 324 mg dose tested on a bi-weekly basis, a mean maximum reduction of 1.37 log10 (p=0.0001) was observed, with a 1.20 log10 mean reduction in viral load (p=0.0001) observed at day 22.
* For the 162 mg weekly dose group, a mean maximum reduction of 0.99 log10 (p=0.0093) was observed, with a 0.75 log10 mean reduction in viral load (p=0.0072) observed at day 22.
Figure 1* depicts the mean change in viral load over time for the four dose groups: for each of the 324 mg dose groups, the mean viral load decreased with each successive treatment, indicating sustained viral suppression by PRO 140.
Subcutaneous PRO 140 was generally well tolerated compared to placebo, with mild and transient local reactions at the site of infusion occurring in a minority of subjects. There were no drug-related serious adverse events and no study discontinuations related to PRO 140.
The poster, Weekly and Biweekly Subcutaneous PRO 140 Demonstrates Potent, Sustained Antiviral Activity, was presented at CROI on February 9, 2009 at 1:00 p.m. ET.
*To view the abstract and poster, as well as a graph depicting the mean change in viral load over time for the four dose groups, please visit the following link: http://www.progenics.com/eventdetail.cfm?eventid=65657
About PRO 140
Discovered by Progenics’ scientists, PRO 140 is a humanized monoclonal antibody that binds to CCR5, a co-receptor characterized by Progenics and its collaborators in 1996 as the principal molecular portal used by HIV to enter and infect immune system cells. Some strains of HIV use the CXCR4 co-receptor as a portal of entry either exclusively or alternatively to CCR5. Unlike small-molecule CCR5 antagonists, PRO 140 inhibits HIV entry at concentrations that in vitro do not appear to block CCR5’s natural activity of directing the migration of immune cells towards sites of inflammation in the body. As a viral-entry inhibitor, PRO 140 is designed to treat HIV by protecting healthy cells from infection. As a monoclonal antibody, PRO 140 is not metabolized by the liver, and therefore may have the potential for a better tolerability profile than many of the existing small-molecule therapies for HIV infection. In February 2006, PRO 140 was designated a Fast Track product by FDA for the treatment of HIV infection.
Progenics gratefully acknowledges the development funding it has received for PRO 140 from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (Public Health Service award: 1 U19 AI066329).
About the Company
Progenics Pharmaceuticals, Inc., of Tarrytown, NY, is a biopharmaceutical company focusing on the development and commercialization of innovative therapeutic products to treat the unmet medical needs of patients with debilitating conditions and life-threatening diseases. Principal programs are directed toward gastroenterology, virology—including human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections—and oncology. Progenics, in collaboration with Wyeth, is developing RELISTOR® (methylnaltrexone bromide) for the treatment of opioid-induced side effects. RELISTOR is currently approved in over 30 countries, which include approvals in the U.S., Canada and Australia, as well as all European Union member countries. In the U.S., RELISTOR (methylnaltrexone bromide) subcutaneous injection is indicated for the treatment of opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Marketing applications are pending for RELISTOR in other countries. In the area of virology, Progenics is developing the HIV entry inhibitor PRO 140, a humanized monoclonal antibody targeting the entry co-receptor CCR5, which is currently in phase 2 clinical testing. The Company is also developing a novel HCV entry inhibitor, PRO 206. In the area of oncology, the Company is conducting a phase 1 clinical trial of a human monoclonal antibody-drug conjugate (ADC) for the treatment of prostate cancer—a selectively targeted cytotoxic antibody directed against prostate-specific membrane antigen (PSMA). PSMA is a protein found on the surface of prostate cancer cells as well as in blood vessels supplying other solid tumors. Progenics is also conducting a phase 1 clinical trial with a vaccine designed to treat prostate cancer by stimulating an immune response to PSMA.
SOURCE: Progenics Pharmaceuticals, Inc.
Post Views: 140
Positive Phase 2 Clinical Results Showed PRO 140 Demonstrated Potent Activity, Favorable Tolerability and the Convenience of Potential Weekly Self-Administration
MONTREAL, CANADA & TARRYTOWN, NY, USA | February 10, 2009 | Progenics Pharmaceuticals, Inc. (Nasdaq: PGNX – News) today announced that it has selected for further development the subcutaneous form of PRO 140 for the treatment of HIV infection. The decision follows positive results from a recently completed phase 2 clinical trial as well as feedback from key opinion leaders, treatment advocates and people living with HIV. Results from the phase 2 study were presented late yesterday at the 16th Conference on Retroviruses and Opportunistic Infections (CROI) in Montreal. In this clinical trial, the subcutaneous dosage form of PRO 140 demonstrated potent and highly significant antiviral effects compared to placebo at all doses of active drug examined and was generally well tolerated.
“These phase 2 clinical results confirm our previously announced interim findings which showed that subcutaneous PRO 140 therapy was potent, long-acting and well tolerated,” said Paul J. Maddon, M.D., Ph.D., Progenics Pharmaceuticals’ Founder, Chief Executive Officer and Chief Science Officer. “We plan to meet with the U.S. Food and Drug Administration to discuss registrational studies for subcutaneous PRO 140. Similar to intravenous PRO 140, the subcutaneous form has demonstrated significant antiviral activity and favorable tolerability in clinical trials to date, with the additional potential benefit of convenient self-administration by patients. Given that all currently available HIV drugs are given between one and three times daily, a weekly therapy could have many advantages related to adherence.”
PRO 140 is a humanized monoclonal antibody that blocks viral infection of healthy cells by binding to CCR5, a co-receptor that is the principal molecular portal used by HIV to enter and infect immune system cells. Some strains of HIV use the CXCR4 co-receptor as a portal of entry either exclusively or in addition to CCR5. CCR5 viral-entry inhibitors, such as PRO 140, are active in blocking infection primarily in HIV patients whose virus uses the CCR5 portal, but do not block the entry of virus that uses the CXCR4 portal.
The data presented yesterday indicate that PRO 140 has the potential to be administered weekly, which may facilitate its use in conjunction with other antiretroviral therapies. In this study, all active doses of subcutaneous PRO 140 demonstrated potent and highly significant antiviral effects compared to placebo. A mean maximum reduction in plasma levels of HIV RNA of 1.65 log10 (98%) was observed following three weekly doses of 324 mg, the highest dose tested. All dose levels were generally well tolerated.
“The results of this clinical trial establish the first ever proof of concept for a long-acting HIV therapy with the potential for self-administration,” said Melanie A. Thompson M.D., Principal Investigator of the AIDS Research Consortium of Atlanta and lead author of the CROI presentation. “Given its favorable tolerability profile and potential for convenient weekly dosing by patients, subcutaneous PRO 140 holds promise in providing a potent and novel treatment option for individuals living with HIV.”
Subcutaneous PRO 140: Summary of phase 2 clinical trial results
In the phase 2 clinical trial of subcutaneous PRO 140, a total of 44 HIV-infected individuals who were treatment naïve or had discontinued therapy for at least three months were randomized to receive three weekly doses of 162 mg PRO 140, two bi-weekly (every-other-week) doses of 324 mg PRO 140, three weekly doses of 324 mg PRO 140, or placebo. Subjects were followed for a total of 58 days for safety and antiviral effects.
In this study, the following activity for PRO 140 was observed:
* For the 324 mg weekly dose group, a mean maximum reduction of 1.65 log10 (p<0.0001) was observed, with a 1.51 log10 mean reduction in viral load (p<0.0001) observed at day 22.
* For the 324 mg dose tested on a bi-weekly basis, a mean maximum reduction of 1.37 log10 (p=0.0001) was observed, with a 1.20 log10 mean reduction in viral load (p=0.0001) observed at day 22.
* For the 162 mg weekly dose group, a mean maximum reduction of 0.99 log10 (p=0.0093) was observed, with a 0.75 log10 mean reduction in viral load (p=0.0072) observed at day 22.
Figure 1* depicts the mean change in viral load over time for the four dose groups: for each of the 324 mg dose groups, the mean viral load decreased with each successive treatment, indicating sustained viral suppression by PRO 140.
Subcutaneous PRO 140 was generally well tolerated compared to placebo, with mild and transient local reactions at the site of infusion occurring in a minority of subjects. There were no drug-related serious adverse events and no study discontinuations related to PRO 140.
The poster, Weekly and Biweekly Subcutaneous PRO 140 Demonstrates Potent, Sustained Antiviral Activity, was presented at CROI on February 9, 2009 at 1:00 p.m. ET.
*To view the abstract and poster, as well as a graph depicting the mean change in viral load over time for the four dose groups, please visit the following link: http://www.progenics.com/eventdetail.cfm?eventid=65657
About PRO 140
Discovered by Progenics’ scientists, PRO 140 is a humanized monoclonal antibody that binds to CCR5, a co-receptor characterized by Progenics and its collaborators in 1996 as the principal molecular portal used by HIV to enter and infect immune system cells. Some strains of HIV use the CXCR4 co-receptor as a portal of entry either exclusively or alternatively to CCR5. Unlike small-molecule CCR5 antagonists, PRO 140 inhibits HIV entry at concentrations that in vitro do not appear to block CCR5’s natural activity of directing the migration of immune cells towards sites of inflammation in the body. As a viral-entry inhibitor, PRO 140 is designed to treat HIV by protecting healthy cells from infection. As a monoclonal antibody, PRO 140 is not metabolized by the liver, and therefore may have the potential for a better tolerability profile than many of the existing small-molecule therapies for HIV infection. In February 2006, PRO 140 was designated a Fast Track product by FDA for the treatment of HIV infection.
Progenics gratefully acknowledges the development funding it has received for PRO 140 from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (Public Health Service award: 1 U19 AI066329).
About the Company
Progenics Pharmaceuticals, Inc., of Tarrytown, NY, is a biopharmaceutical company focusing on the development and commercialization of innovative therapeutic products to treat the unmet medical needs of patients with debilitating conditions and life-threatening diseases. Principal programs are directed toward gastroenterology, virology—including human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections—and oncology. Progenics, in collaboration with Wyeth, is developing RELISTOR® (methylnaltrexone bromide) for the treatment of opioid-induced side effects. RELISTOR is currently approved in over 30 countries, which include approvals in the U.S., Canada and Australia, as well as all European Union member countries. In the U.S., RELISTOR (methylnaltrexone bromide) subcutaneous injection is indicated for the treatment of opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Marketing applications are pending for RELISTOR in other countries. In the area of virology, Progenics is developing the HIV entry inhibitor PRO 140, a humanized monoclonal antibody targeting the entry co-receptor CCR5, which is currently in phase 2 clinical testing. The Company is also developing a novel HCV entry inhibitor, PRO 206. In the area of oncology, the Company is conducting a phase 1 clinical trial of a human monoclonal antibody-drug conjugate (ADC) for the treatment of prostate cancer—a selectively targeted cytotoxic antibody directed against prostate-specific membrane antigen (PSMA). PSMA is a protein found on the surface of prostate cancer cells as well as in blood vessels supplying other solid tumors. Progenics is also conducting a phase 1 clinical trial with a vaccine designed to treat prostate cancer by stimulating an immune response to PSMA.
SOURCE: Progenics Pharmaceuticals, Inc.
Post Views: 140
